Positive pressure systems and methods for increasing blood pressure and circulation

ABSTRACT

In one embodiment, the invention provides a medical method for treating a person and comprises repeatedly compressing the person&#39;s chest. While repeatedly compressing the person&#39;s chest, the method further includes repeatedly delivering a positive pressure breath to the person and extracting respiratory gases from the person&#39;s airway using a vacuum following the positive pressure breath to create an intrathoracic vacuum to lower pressures in the thorax and to enhance blood flow back to the heart.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/034,996 (now U.S. Pat. No. 7,766,011) and is a continuation in partapplication of U.S. patent application Ser. No. 10/796,875, filed Mar.8, 2004. This application is also a continuation in part application ofU.S. patent application Ser. No. 10/660,462, filed Sep. 11, 2003 (nowU.S. Pat. No. 7,082,945), which is a continuation in part application ofU.S. patent application Ser. No. 10/460,558, filed Jun. 11, 2003 (nowU.S. Pat. No. 7,185,649), which is a continuation-in-part of U.S. patentapplication Ser. No. 10/426,161, filed Apr. 28, 2003 (now U.S. Pat. No.7,195,012), the complete disclosures of which are herein incorporated byreference.

This application is also related to U.S. patent application Ser. No.10/765,318, filed Jan. 26, 2004 (now U.S. Pat. No. 7,195,013), thecomplete disclosure of which is herein incorporated by reference.

BACKGROUND OF THE INVENTION

This invention relates generally to the field of systemic, intracranialand intraocular pressures. More specifically, the invention relates todevices and methods for decreasing intracranial and intraocularpressures and increasing systemic arterial pressures and systemic vitalorgan perfusion, such as those resulting from a traumatic head injury,blood loss, and other injuries and illnesses that cause low bloodpressure and poor circulation. The invention provides a means tomaintain adequate blood pressure and ventilation in a patient who haslow blood pressure and is unable to breathe independently in order tomaintain vital organ perfusion and oxygenation.

Decreased organ perfusion results in cell death. Both low systemicpressures, or in the case of the brain, high intracranial pressuresreduce vital organ perfusion. Hence, head trauma and shock are generallyregarded as the leading cause of morbidity and mortality in the UnitedStates for children and young adults. Head trauma often results inswelling of the brain. Because the skull cannot expand, the increasedpressures within the brain can lead to death or serious brain injury.While a number of therapies have been evaluated in order to reduce brainswelling, including use of hyperventilation and steroids, an effectiveway to treat intracranial pressures remains an important medicalchallenge. Similarly, low blood pressure and multi-organ injury decreasevital organ perfusion and when associated with head trauma there is anincrease in pressure within the brain and a subsequent decrease incerebral blood flow. These patients have an extremely high mortalityrate and similarly remain a major medical challenge.

BRIEF SUMMARY OF THE INVENTION

In one embodiment, the invention provides a device for decreasingintracranial or intraocular pressures and increasing systemic bloodpressures and organ perfusion. The device comprises a housing having aninlet opening and an outlet opening that is adapted to be interfacedwith a person's airway. The device further includes a valve system thatis operable to regulate respiratory gas flows through the housing andinto the person's lungs during spontaneous or artificial inspiration.For a person who requires artificial inspiration, the valve system canbe attached to a vacuum source. The valve system assists in loweringintrathoracic pressures during spontaneous inspiration and innon-breathing patients when not actively delivering a breath to in turnlower intracranial pressures or intraocular pressures and increasesystemic perfusion pressures. The valve system may also be used tocontinuously or intermittently lower pressures in the head by loweringthe pressures within the thorax. In addition, the invention lowers thepressures within the left and right heart, when positive pressureventilations are not being provided. The reduced pressures in thethorax, including the heart, draws more blood back to the heart therebyhelping to increase the efficiency of heart function and cardiac output.The invention can therefore be used to treat patients suffering from anumber of disease states including but not limited to those sufferingfrom elevated intracranial pressures, intra-ocular pressures, shock,hypotension, circulatory collapse, cardiac arrest, those in dialysis andheart failure. The invention is based upon the discovery that reductionsin intrathoracic pressure result in a decrease in intracranial pressuresand enhancement of blood flow to the heart.

Such a device may also be used to facilitate movement of cerebral spinalfluid. In so doing, intracranial pressures may be further reduced. Sucha device may therefore be used to treat those suffering from head traumaassociated with elevated intracranial pressures as well as thosesuffering from conditions that cause low systemic blood pressure.

In one aspect, the valve system is configured to open to permitrespiratory gasses to freely flow to the person's lungs duringspontaneous respirations when the negative intrathoracic pressurereaches a pressure in the range from about −2 cmH2O to about −20 cmH2Oin order to reduce intrathoracic pressure and thus reduce intracranialor intraocular pressures. In this way, the negative intrathoracicpressure is lowered until a threshold pressure is reached, at which timethe valve opens. The cycle may be repeated continuously or periodicallyto repetitively lower intrathoracic pressures. In another aspect, thevalve system is configured to generate an intrathoracic vacuum in therange from about −2 cm H2O to about −20 cm H2O in order to both reduceintrathoracic pressure and thus reduce intracranial or intraocularpressures and to enhance blood flow to the heart. The device may includemeans for repetitively compressing the chest to improve bloodcirculation in patents in or with low blood circulation or cardiacarrest. The compression could be accomplished with an automated chestcompression, a circumferential vest, and the like. This would improveblood flow to the heart and brain in patients with low bloodcirculation. When the device compresses the chest blood is forced out ofthe heart to increase perfusion of the vital organs. When thecompression means is released, blood flows back into the heart. In somecases, a decompression device could also be used to actively lift ordecompress the chest to enhance the blood flow back to the heart.

The device may also include means for causing the person to artificiallyinspire through the valve system. For example, the device may utilize anelectrode, an iron lung cuirass device, a chest lifting device, aventilator or the like. By reducing the pressure within the chest,respiratory gases flow into the lungs and provide oxygen. Bysequentially compressing the chest and then decompressing the chest, thechest is turned into a bellows and blood is circulated and respiratorygases are exchanged. This action can be timed with the naturalcontractions of the heart, such as by using an ECG. In one embodiment,the chest is compressed and then the chest is allowed to recoil to itsresting position to circulate blood and respiratory gases. After eachchest wall recoil, a device is used to lower intrathoracic pressures tocreate an intrathoracic vacuum to enhance blood flow back to the heart.In another embodiment, the chest is compressed and then activelydecompressed to circulate blood and respiratory gases, and after eachchest decompression a device is used to lower intrathoracic pressures tocreate an intrathoracic vacuum to enhance blood flow back to the heartand also lower intracranial pressures. Devices that may be used to lowerintrathoracic pressures include any type of vacuum, including thoseincorporated into a ventilator. During at least some of thedecompressions, respiratory gases may be permitted to freely flow to thelungs to provide proper ventilation.

In another embodiment, the device may comprise a means to reduceintrathoracic pressure by applying a vacuum within the airway. Thevacuum may be adjusted in terms of frequency, amplitude, and duration.This results in a decrease in intracranial pressure in proportion to thedegree of vacuum applied. Hence, intracranial pressures may be reducedsimply by manipulating airway pressures to reduce intrathoracicpressures. In addition, the vacuum created within the thorax enhancesblood flow back to the heart, thereby simultaneously increasing cardiacoutput and systemic vital organ perfusion. Such a vacuum may begenerated from an external vacuum source, through the airway or a chesttube between the ribs, or it may be generated using a ventilator capableof applying a negative pressure.

The device may further include a mechanism for varying the level ofimpedance or resistance of the valve system. It may include addingpositive expiratory pressure when the chest is being compressed. Thisdevice may be used in combination with at least one physiological sensorthat is configured to monitor at least one physiological parameter ofthe person. In this way, the mechanism for varying the level ofimpedance intrathoracic pressure may be configured to receive signalsfrom the sensor and to vary the level of impedance of the valve systembased on the signals. Examples of sensors that may be used include thosethat measure respiratory rate, intrathoracic pressure, intratrachealpressure, blood pressure, right heart pressure, heart rate, end tidalCO₂, oxygen level, intracranial perfusion, and intracranial pressure.

In one aspect, a coupling mechanism may be used to couple the valvesystem to the person's airway. Examples of coupling mechanisms include amouthpiece, an endotracheal tube, and a face mask.

A wide variety of valve systems may be used to repetitively decrease theperson's intrathoracic pressure. For example, valve systems that may beused include those having spring-biased devices, those having automated,electronic or mechanical systems to occlude and open a valve lumen, duckbill valves, ball valves, other pressure sensitive valve systems capableof opening a closing when subjected to low pressure differentialstriggered either by spontaneous breathing and/or external systems tomanipulate intrathoracic pressures (such as ventilators, phrenic nervestimulators, iron lungs, and the like).

In another embodiment, the invention provides a method for decreasingintracranial or intraocular pressures. According to the method, a valvesystem is coupled to a person's airway and is configured to at leastperiodically reduce or prevent respiratory gases from flowing to theperson's lungs. With the valve system coupled to the airway, theperson's negative intrathoracic pressure is repetitively decreased to inturn repetitively lower pressures in the venous blood vessels thattransport blood out of the head. In so doing, intracranial andintraocular pressures are reduced. Such a method also facilitatesmovement of cerebral spinal fluid. In so doing, intracranial pressuresare further reduced. As such, this method may also be used to treat aperson suffering from head trauma that is associated with elevatedintracranial pressures, those suffering from heart conditions thatincrease intracranial pressures, such as atrial fibrillation and heartfailure, and those suffering from low blood pressure that is caused inpart or whole by a decrease in cardiac output or function.

The person's negative intrathoracic pressure may be repetitivelydecreased as the person repeatedly inspires through the valve system.This may be done by the person's own efforts (referred to as spontaneousbreathing), or by artificially causing the person to repeatedly inspirethrough the valve system. For example, the person's intrathoracicpressure can be lowered by repeatedly stimulating the phrenic nerve, bymanipulating the chest with an iron lung cuirass device, by generatingnegative pressures within the thorax using a ventilator, by applying avacuum within the thorax that can be regulated by the valve system, byapplying a high frequency ventilator that supplies oscillations at arate of about 200 to about 2000 per minute, or the like. Lowering theintrathoracic pressure can be used to draw respiratory gases into thelungs, draw more blood back to the heart, or both. Lowering theintrathoracic pressure can also be used to lower intracranial andintraocular pressures.

In another aspect, the level of impedance of the valve system may befixed or variable. If variable, at least one physiological parameters ofthe person may be measured, and the impedance level may be varied basedon the measured parameters.

To couple the valve system to the airway, a variety of techniques may beused, such as by using a mouthpiece, an endotracheal tube, a face maskor the like. Further, the respiratory gases may be prevented fromentering the lungs through the valve system until a negativeintrathoracic pressure in the range from about 0 cmH2O to about −25cmH2O is achieved, at which time the valve system permits respiratorygases to flow to the lungs.

In another embodiment, the invention provides a method for treating aperson suffering from head trauma associated with elevated intracranialpressures. According to the method, a positive pressure breath isdelivered to the person. Respiratory gases are extracted from theperson's airway by a vacuum source attached to a device situated betweenthe ventilator and the person's airway to create an intrathoracicvacuum. In turn, this reduces intracranial pressures and may also lowerpressures in the venous blood vessels that transport blood out of thehead. In some options positive pressure breaths are delivered to thelungs to provide respiratory gases. The steps of delivering positivepressure breaths and extracting respiratory gases are repeated tocontinue the treatment. Further, a positive pressure breath need not beprovided every time before extracting gases, but only when needed toprovide proper ventilation. In some cases, blood volume may be reducedby the use of diuretics or other means including but not limited tointentional blood loss or volume depletion to enhance the effects oflowering intracranial pressures by lowering intrathoracic pressures.

In some options, the patient may also have his or her intrathoracicpressures externally manipulated with an external thoracic positivepressure source while being provided with the positive pressure breathsand the extraction of gases from the airway. Examples of externalthoracic positive pressure sources include a mechanical extrathoracicvest, a body cuirass, a compression piston, a compression cup and thelike. These devices may be supplied with energy from a variety ofsources, such as pneumatic, electric, combustion and the like. Further,the external compressions may be timed with cardiac activity, e.g., withECG activity. Further, the external compressions and/or application ofthe positive pressure breath and the vacuum may be used in combinationwith invasive means to maintain blood pressure, such as by removingblood from the patient. Also, in some cases, the patient's chest mayalso need to at least periodically be decompressed. In such cases, avalve may be placed in the patient's airway to prevent air from rushinginto the patient's lungs for at least some time in order to increase themagnitude of the negative intrathoracic pressure that is created.

In one aspect, the delivery of the positive pressure breaths and theextraction of gases are performed using a mechanical ventilator. Therespiratory gases may be extracted with a constant extraction or apulsed extraction.

In a further aspect, the breath may be delivered for a time in the rangefor about 250 milliseconds to about 2 seconds. Also, the breath may bedelivered at a rate in the range from about 0.1 liters per second toabout 5 liters per second. In another aspect, the vacuum may bemaintained at a pressure in the level from about 0 mmHg to about −50mmHg. The vacuum may be maintained with a negative flow or without anyflow. The time that the positive pressure breath is supplied relative tothe time in which respiratory gases are extracted may be in the rangefrom about 0.5 to about 0.1.

A variety of equipment may be used to extract the respiratory gasesincluding mechanical ventilators, phrenic nerve stimulators, ventilatorbags, a vacuum attached to the airway device, iron lung cuirass devices,a chest tube, and the like. In some cases, a threshold valve may also becoupled to the person's airway. The threshold valve may be configured toopen when an adult's negative intrathoracic pressure exceeds about −3cmH2O. For pediatric cases, the valve may open when the pressure exceedsabout −2 cmH2O to about −5 cmH2O. In this way, when the person inhales,the negative intrathoracic pressure may be lowered.

A variety of schemes may be used to deliver and extract respiratorygases. For example, respiratory gases may be extracted to achieve apressure of about −5 mmHg to about −10 mmHg and then kept generallyconstant until the next positive pressure breath. As another example,the positive breath may be slowly delivered and the intrathoracicpressure may be rapidly lowered to a pressure of about −10 mmHg to about−20 mmHg and then gradually increased towards about 0 mmHg. As a furtherexample, the intrathoracic pressure may be slowly lowered to a pressureof about −20 mm Hg.

In a further embodiment, the invention provides a device for loweringintrathoracic pressures. The device comprises a housing having aninterface that is adapted to couple the housing to the person's airway.A vacuum source is in fluid communication with the housing forrepeatedly extracting respiratory gases from the person's lungs andairway to create and periodically maintain a negative intrathoracicpressure. A vacuum regulator is used to regulate the extraction ofrespiratory gases from the patient's lungs and airway. Also, a positivepressure source is in fluid communication with the housing forintermittently supplying positive pressure breaths to the person ifneeded. Such a device may be used to treat a variety of ailments, suchas head trauma associated with elevated intracranial pressures, lowblood pressure, low blood circulation, low blood volume, cardiac arrestand heart failure.

In some cases, a switching mechanism may be used to stop the extractionof respiratory gases or to deliver of a positive pressure breath. Avariety of switching mechanisms may be used, such as mechanical devices,magnetic devices, and electronic devices. Also, a variety of vacuumsources may be used to extract the respiratory gases, including amechanical ventilator, a vacuum with vacuum regulator, a phrenic nervestimulator, an extrathoracic vest, a ventilator bag, and an iron lungcuirass device, a suction line, a venturi device attached to an oxygentank and the like.

To regulate the vacuum, a threshold valve may be placed in fluidcommunication with the person's airway. The threshold valve may beconfigured to open when the person's negative intrathoracic pressurereaches about −3 cm H2O to about −20 cm H2O to permit respiratory gasesto flow into the person's airway. Also, a variety of pressure sourcesmay be used to deliver a positive pressure breath, such as a mechanicalventilator, a hand held bag valve resuscitator, mouth-to-mouth, or ameans to provide intermittent positive pressure ventilation. A varietyof gauges may be incorporated into the device that are coupled tosensors to measure, for example, the vacuum pressure applied to thepatient and other physiological measures such as the intratrachealpressure or intracranial pressure.

In one specific aspect, the invention provides methods and devices thatallow the chest to be compressed and decompressed, akin to transformingthe chest into a bellows. A wide variety of devices or systems may beused to compress and decompress the chest as described herein. Further,an impedance valve and/or intrathoracic vacuum regulator may be used tolower intrathoracic pressures within the chest when not activelycompressing or decompressing the chest to enhance blood flow black tothe heart and lower intracranial pressures. Optionally, the device mayhave the capability to provide periodic positive pressure ventilations.In one particular option, the compressions may be timed with the heartbeat, such as by using an ECG. Also, the decompressions could happenedless often than after every compression. For example, the chest may bedecompressed about 6 to about 30 times a minute to provide propernegative pressure ventilations, i.e., the creation of a vacuum withinthe thoracic to naturally inspire air through an unimpeded airway, suchas by the use of an iron lung, phrenic nerve stimulation, a suction cupadhered to the chest, and the like. Such a device thus provides a way toartificially maintain blood pressure and ventilation, by negativepressure ventilation and/or by positive pressure ventilations. Thedevice also enhances vital organ circulation and lowers intracranialpressures in patients with low blood pressure who may or may not be ableto breathe as well.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow chart illustrating one method for reducing intracranialand intraocular pressures according to the invention.

FIG. 2 is a perspective view of one embodiment of a facial mask and avalve system that may be used to reduce intracranial and intraocularpressures according to the invention.

FIG. 3 is a perspective view of the valve system of FIG. 2.

FIG. 4 is a cross sectional side view of the valve system of FIG. 3.

FIG. 5 is an exploded view of the valve system of FIG. 3.

FIG. 6 is a schematic diagram of a system for reducing intracranial andintraocular pressures according to the invention.

FIG. 7 is a series of graphs illustrating the lowering of intracranialpressures in an animal study.

FIG. 8 is a series of graphs illustrating the lowering of intracranialpressures in another animal study.

FIG. 9A is a schematic diagram of a person's brain under normalconditions.

FIG. 9B illustrates the brain of FIG. 9A after increased swelling.

FIG. 10 shows three graphs illustrating the effect of loweringintrathoracic pressure on intracranial pressure and right atrialpressure.

FIG. 11 is a flow chart illustrating another method for reducingintracranial and intraocular pressures according to the invention.

FIGS. 12A-12C show three graphs illustrating patterns for delivering apositive pressure breath and extracting respiratory gases according tothe invention.

FIGS. 13A and 13B schematically illustrate one device that may be usedto lower intrathoracic pressures with a non-breathing patient accordingto the invention.

FIGS. 14A and 14B illustrate another device that may be used to lowerintrathoracic pressures with a non-breathing patient according to theinvention.

FIGS. 15A and 15B illustrate one embodiment of a threshold valve systemthat may be used with the device of FIGS. 14A and 14B.

DETAILED DESCRIPTION OF THE INVENTION

In a broad sense, the invention provides devices and techniques forlowering intracranial and intraocular pressures and increasing cerebralperfusion pressures. Such devices and techniques may be particularlyhelpful with patients who have suffered a traumatic brain injury andthose with low blood flow states and low blood pressure. Examples ofconditions that may be treated include hypotension, shock secondary tohypovolemia, sepsis, heart failure, and the like. One way to lower thepressure within the head but maintain or increase systemic pressures isby using a valve system that is coupled to a person's airway and that isused to lower intrathoracic pressures. In so doing, the valve systemsmay be used to accelerate the removal of venous blood from the brain,thereby decreasing intracranial and intraocular pressures. At the sametime, the systemic pressures increase due to enhancement of venousreturn to the heart. Other techniques may be used as well, such as bycreating a vacuum intermittently within the thorax and/or by repeatedlycompressing and/or decompressing the patient's chest using an externalthoracic positive pressure source. By reducing intracranial pressures,movement of cerebral spinal fluid is also enhanced. In so doing,intracranial pressures are further reduced thereby providing furthertreatment for those suffering from head trauma. In some cases, the valvesystems may also be used to treat the brain function in a personsuffering from a heart condition (atrial fibrillation, heart failure,cardiac tamponade, and the like) that results in elevated intracranialpressures. Such heart conditions may include, for example, atrialfibrillation or heart failure. By reducing intracranial pressures,cerebral spinal fluid movement and translocation is increased to helpimprove brain function.

Intracranial pressures are regulated by the amount the cerebralperfusion pressure, which is determined by the arterial blood pressureto the head, the pressures within the skull, and the pressures withinthe venous system that drains blood flow from the brain. The devices andmethods of the invention may be used to enhance the egress of venousblood out of the brain, thereby lowering intracranial pressures. Thedevices and methods can be used in patients that are breathingspontaneously and those that require assisted ventilation. To do so, thedevices and methods may be used to augment the intrathoracic vacuumeffect each time a patient inhales (or in the case of a non-breathingpatient, each time the pressure within the chest is manipulated to fallbelow atmospheric pressure), thereby lowering the pressures in thethorax and in the venous blood vessels that transport blood out of thebrain. The vacuum effect is transduced back into the brain, and as aresult, intracranial pressures are lowered with each inspiratory effort.This in turn causes more venous blood to flow out of the head than wouldotherwise be possible, resulting in lower intracranial pressures andlower intraocular pressures. In addition, circulation to the vitalorgans is increased as the increase in venous return to the heart eachtime a negative intrathoracic pressure is generated results in anincrease in cardiac output and improved vital organ perfusion. As such,this invention may be used to help patients suffering from low cardiacoutput states and low blood pressure.

To prevent or impede respiratory gases from flowing to the lungs, avariety of impeding or preventing mechanisms may be used, includingthose described in U.S. Pat. Nos. 5,551,420; 5,692,498; 6,062,219;5,730,122; 6,155,257; 6,234,916 and 6,224,562, and in U.S. patentapplication Ser. Nos. 10/224,263, filed on Aug. 19, 2002 (“Systems andMethods for Enhancing Blood Circulation”, Attorney Docket No.16354-000115), 10/401,493, filed Mar. 28, 2003 (“Diabetes TreatmentSystems and Methods”, Attorney Docket No. 16354-000116), 09/966,945,filed Sep. 28, 2001 and 09/967,029, filed Sep. 28, 2001, the completedisclosures of which are herein incorporated by reference. The valvesystems may be configured to completely prevent or provide resistance tothe inflow of respiratory gases into the patient while the patientinspires. For valve systems that completely prevent the flow ofrespiratory gases, such valves may be configured as pressure responsivevalves that open after a threshold negative intrathoracic pressure hasbeen reached.

For example, the resistance to the inflow of respiratory gases may beset between about 0 cm H2O and about −25 cm H2O and may be variable orfixed. More preferably, the valve system may be configured to open whenthe negative intrathoracic pressure is in the range from about −2 cmH2Oto about −20 cmH2O. In addition, the valve system may used continuouslyor on a variable basis. For example, the valve system may be used forevery other spontaneous breath.

Although not intended to be limiting, specific kinds of impedance valvesthat may be used to reduce intracranial and intraocular pressuresinclude those having spring-biased devices, automated/electronic andmechanical means to occlude and open a valve lumen, duck bill valves,ball valves, and other pressure sensitive valve systems capable ofopening and closing when subjected to low pressure differentialstriggered either by spontaneous breathing and/or external means tomanipulate intrathoracic pressure (such as ventilators, phrenic nervestimulators, an iron lung, and the like).

In the past, such threshold valve systems have been used to increase thevenous preload on the heart and to increase cardiac output, strokevolume and blood pressure because of the augmented effects of theintrathoracic vacuum on the subsequent cardiac contraction. In contrast,the techniques of the invention function by facilitating the removal ofblood from the venous side of the brain. Although there may be anincrease in blood flow out of the heart to the vital organs (includingto the brain) when using such valve systems, the effect of the valvesystems on lowering of intracranial pressures was quite unexpectedbecause of the known increase in blood flow to the brain. Remarkably,however, the reduction of venous blood pressures from the brain remainssubstantial when using the valve systems. Thus, despite the increase inblood flow to the brain, the net effect of the valve system is adecrease in intracranial pressures.

With the valve system coupled to the person's airway, the negativeintrathoracic pressure may be enhanced by inspiring through the valvesystem. If the person is spontaneously breathing, the person may simplybreath through the valve system. If the person is not breathing,artificial inspiration may be induced using a variety of techniques,including electrical stimulation of the diaphragm, a negative pressureventilator such as a body cuirass or iron lung, or a positive pressureventilator capable of also generating a vacuum between positive pressureventilations. As one example, at least some of the respiratory muscles,and particularly the inspiratory muscles, may be stimulated to contractin a repeating manner in order to cause the person to inspire throughthe valve system, thereby increasing the magnitude and prolonging theduration of negative intrathoracic pressure, i.e., respiratory musclestimulation increases the duration and degree that the intrathoracicpressure is below or negative with respect to the pressure in theperipheral venous vasculature. Upon contraction of the respiratorymuscles, the patient will typically “gasp”. These techniques may beperformed alone, or in combination with a valve system.

Among the respiratory muscles that may be stimulated to contract are thediaphragm, the chest wall muscles, including the intercostal muscles andthe abdominal muscles. Specific chest wall muscles that may bestimulated to contract include those that elevate the upper ribs,including the scaleni and sternocleidomastoid muscles, those that act tofix the shoulder girdle, including the trapezii, rhomboidei, andlevatores angulorum scapulorum muscles, and those that act to elevatethe ribs, including the serrati antici majores, and the pectoralesmajores and minores as described generally in Leslie A. Geddes,“Electroventilation—A Missed Opportunity?”, Biomedical Instrumentation &Technology, July/August 1998, pp. 401-414, the complete disclosure ofwhich is herein incorporated by reference. Of the respiratory muscles,the two hemidiaphragms and intercostal muscles appear to be the greatestcontributors to inspiration and expiration. The respiratory muscles maybe stimulated to contract in a variety of ways. For example, thediaphragm may be stimulated to contract by supplying electrical currentor a magnetic field to various nerves or muscle bundles which whenstimulated cause the diaphragm to contract. Similar techniques may beused to stimulate the chest wall muscles to contract. A variety of pulsetrains, pulse widths, pulse frequencies and pulse waveforms may be usedfor stimulation. Further, the electrode location and timing of pulsedelivery may be varied. In one particular aspect, an electrical currentgradient or a magnetic field is provided to directly or indirectlystimulate the phrenic nerve.

To electrically stimulate the inspiratory motor nerves, electrodes arepreferably placed on the lateral surface of the neck over the pointwhere the phrenic nerve, on the chest surface just lateral to the lowersternum to deliver current to the phrenic nerves just as they enter thediaphragm, on the upper chest just anterior to the axillae to stimulatethe thoracic nerves, in the oral pharyngeal region of the throat, or onthe larynx itself. However, it will be appreciated that other electrodesites may be employed. For example, in one embodiment the respiratorymuscles are stimulated by a transcutaneous electrical impulse deliveredalong the lower antero-lat margin of the rib cage. In one embodiment,inspiration is induced by stimulating inspiratory muscles using one ormore electrodes attached to an endotracheal tube or pharyngeal tube. Tostimulate the diaphragm, the phrenic nerve may be stimulated in the neckregion near C3-C7, such as between C3, C4 or C5, or where the phrenicnerves enter the diaphragm. Alternative techniques for stimulatingdiaphragmatic contraction include magnetic field stimulation of thediaphragm or the phrenic nerve. Magnetic field stimulation may also beemployed to stimulate the chest wall muscles. Electrical fieldstimulation of the diaphragm or the chest wall muscles may beaccomplished by placing one or more electrodes on the skin, preferablyin the vicinity of the neck or the lower rib cage (although otherlocations may be employed) and then providing an electrical voltagegradient between electrodes that induces transcutaneous current flow tostimulate the respiratory muscles to contract. Still further,subcutaneous electrodes may also be used to stimulate respiratory musclecontraction. Other techniques are described in U.S. Pat. No. 6,463,327,the complete disclosure of which is herein incorporated by reference.

The valve systems may have a fixed actuating pressure or may be variableso that once a desired negative intrathoracic pressure is reached, theresistance to flow may be lessened. Further, the valves of the inventionmay be configured to be variable, either manually or automatically. Theextent to which the resistance to flow is varied may be based onphysiological parameters measured by one or more sensors that areassociated with the person being treated. As such, the resistance toflow may be varied so that the person's physiological parameters arebrought within an acceptable range. If an automated system is used, suchsensors may be coupled to a controller which is employed to control oneor more mechanisms that vary the resistance or actuating pressure of theinflow valve as generally described in the references that have beenincorporated by reference.

Hence, the valve systems of the invention may also incorporate or beassociated with sensors that are used to detect changes in intrathoracicpressures or other physiological parameters. In one aspect, the sensorsmay be configured to wirelessly transmit their measured signals to aremote receiver that is in communication with a controller. In turn thecontroller may use the measured signals to vary operation of the valvesystems described or incorporated by reference herein. For example,sensors may be used to sense blood pressure, pressures within the heart,intrathoracic pressures, positive end expiratory pressure, respiratoryrate, intracranial pressures, intraocular pressures, respiratory flow,oxygen delivery, temperature, blood pH, end tidal CO2, tissue CO2, bloodoxygen, cardiac output or the like. Signals from these sensors may bewirelessly transmitted to a receiver. This information may then be usedby a controller to control the actuating pressure or the resistance ofan inflow valve as described in the references incorporated herein byreference.

The techniques for reducing intracranial pressures may be used in avariety of settings. For example, the techniques may be used in person'swho are spontaneously breathing, those who are not breathing but whosehearts are beating, and those in cardiac arrest. In the latter case, thetechniques may use some means to create a vacuum intermittently withinthe thorax during the performance of CPR. This could be by using a valvesystem or some other type of pressure manipulation system. Further, suchsystems may be used in other settings as well, including when the personis breathing.

FIG. 1 is flow diagram illustrating one method for reducing intracranialor intraocular pressures. As shown in step 10, the process proceeds bycoupling a valve system to the person's airway. Any kind of couplingmechanism may be used, such as by a mouthpiece, an endotracheal tube, aface mask, or the like. Further, any of the valve systems described orincorporated herein by reference may be used. In step 20, the person'snegative intrathoracic pressure is repetitively decreased (eitherartificially or by spontaneous breathing). Examples of techniques toartificially reduce the negative intrathoracic pressure include use ofan iron lung cuirass device, a ventilator that is capable of generatingnegative pressures, a ventilator that is capable of providing highfrequency oscillations at a rate of about 200 to about 2000 per minute,a phrenic nerve stimulator, or the like. As the person's negativeintrathoracic pressure is repeatedly decreased while the valve system iscoupled to the airway, the pressures in the venous vessels thattransport blood out of the head are also lowered. In so doing,intracranial and intraocular pressures are reduced.

As shown in step 30, various physiological parameters of the person mayoptionally be measured. Examples of such parameters include respiratoryrate, intrathoracic pressure, intertracheal pressure, intracranialpressure, intracranial blood flow, intraocular pressure, blood pressure,heart rate, end tidal CO₂, oxygen saturation, and the like. Further, asshown in step 40, the valve system's actuating threshold level mayoptionally be varied based on the measured physiological parameters.This may be done to maximize the amount of blood drawn out of the brainor simply to monitor the patient's condition to insure that the patientremains stable.

FIG. 2 illustrates one embodiment of a facial mask 100 to which iscoupled a valve system 200. Mask 100 is configured to be secured to apatient's face so as to cover the mouth and nose. Mask 100 and valvesystem 200 are examples of one type of equipment that may be used tolower intrathoracic pressures and thereby lower intracranial andintraocular pressures. However, it will be appreciated that other valvesystems and other coupling arrangements may be used including, forexample, those previously referenced. As such the invention is notintended to be limited to the specific valve system and mask describedbelow.

Referring also to FIGS. 3-5, valve system 200 will be described ingreater detail. Valve system 200 includes a valve housing 202 with asocket 204 into which a ball 206 of a ventilation tube 208 is received.In this way, ventilation tube 208 may rotate about a horizontal axis andpivot relative to a vertical axis. A respiratory source, such as aventilation bag, may be coupled to tube 208 to assist in ventilation.Disposed in ventilation tube 208 is a filter 210 that is spaced above aduck bill valve 212. A diaphragm holder 214 that holds a diaphragm 216is held within housing 202. Valve system 200 further includes a patientport 218 that is held in place by a second housing 220. Housing 220conveniently includes tabs 222 to facilitate coupling of valve system200 with facial mask 100. Also held within housing 220 is a check valve224 that comprises a spring 224 a, a ring member 224 b, and an o-ring224 c. Spring 224 a biases ring member 224 b against patient port 218.Patient port 218 includes bypass openings 226 that are covered by o-ring224 c of check valve 224 until the pressure in patient port 218 reachesa threshold negative pressure to cause spring 224 a to compress.

When the patient is actively ventilated, respiratory gases are forcedthrough ventilation tube 208. The gases flow through filter 210, throughduck bill valve 212, and forces up diaphragm 214 to permit the gases toexit through port 218. Hence, at any time the patient may be ventilatedsimply by forcing the respiratory gases through tube 208.

During the exhalation phase of a breathing cycle, expired gases flowthrough port 218 and lift up diaphragm 214. The gases then flow througha passage 227 in ventilation tube 208 where they exit the system throughopenings 229 (see FIG. 3).

During the inhalation phase of a breathing cycle, valve system 200prevents respiratory gases from flowing into the lungs until a thresholdnegative intrathoracic pressure level is exceeded. When this pressurelevel is exceeded, check valve 224 is pulled downward as springs 224 aare compressed to permit respiratory gases to flow through openings 226and to the patient's lungs by initially passing through tube 208 andduck bill valve 212. Valve 224 may be set to open when the negativeintrathoracic pressure is in the range from about 0 cm H2O to about −25cm H2O, and more preferably from about −2 cm H2O to about −−20 cm H2O.Hence, the magnitude and duration of negative intrathoracic pressure maybe enhanced during patient inhalation by use of valve system 200. Oncethe intrathoracic pressure falls below the threshold, recoil spring 224a again close check valve 224. In this way, pressure within the venousblood vessels that transport blood out of the brain are also lowered. Inso doing, more blood is drawn out of the brain to reduce intracranialand intraocular pressures.

Any of the valve systems described herein may be incorporated into atreatment system 300 as illustrated in FIG. 6. System 300 mayconveniently include facial mask 100 and valve system 200, although anyof the valve systems or interfacing mechanisms described herein or thelike may be used, including but not limited to the valve system of FIG.14. Valve system 200 may conveniently be coupled to a controller 310. Inturn, controller 310 may be used to control the impedance level of valvesystem 200 in a manner similar to any of the embodiments described orincorporated herein. The level of impedance may be varied based onmeasurements of physiological parameters, or using a programmed scheduleof changes. System 300 may include a wide variety of sensors and/ormeasuring devices to measure any of the physiological parametersdescribed herein. These sensors or measuring devices may be integratedwithin or coupled to valve system 200 or facial mask, or may beseparate.

For example, valve system 200 may include a pressure transducer fortaking pressure measurements (such as intrathoracic pressures,intracranial pressures, intraocular pressures), a flow rate measuringdevice for measuring the flow rate of air into or out of the lungs, or aCO2 sensor for measuring expired CO2.

Examples of other sensors or measuring devices include a heart ratesensor 330, a blood pressure sensor 340, and a temperature sensor 350.These sensors may also be coupled to controller 310 so that measurementsmay be recorded. Further, it will be appreciated that other types ofmeasuring devices may be used to measure various physiologicalparameters, such as oxygen saturation and/or blood levels of O2, bloodlactate, blood pH, tissue lactate, tissue pH, blood pressure, pressureswithin the heart, intrathoracic pressures, positive end expiratorypressure, respiratory rate, intracranial pressures, intraocularpressures, respiratory flow, oxygen delivery, temperature, end tidalCO2, tissue CO2, cardiac output or the like.

In some cases, controller 310 may be used to control valve system 200,to control any sensors or measuring devices, to record measurements, andto perform any comparisons. Alternatively, a set of computers and/orcontrollers may be used in combination to perform such tasks. Thisequipment may have appropriate processors, display screens, input andoutput devices, entry devices, memory or databases, software, and thelike needed to operate system 300.

A variety of devices may also be coupled to controller 310 to cause theperson to artificially inspire. For example, such devices may comprise aventilator 360, an iron lung cuirass device 370 or a phrenic nervestimulator 380. Ventilator 360 may be configured to create a negativeintrathoracic pressure within the person, or may be a high frequencyventilator capable of generating oscillations at about 200 to about 2000per minute.

Example 1

The following is a non-limiting example illustrating how intracranialpressures may be lowered according to the invention. In this example, 30kg pigs were anesthetized with propofol. Using a micromanometer-tippedelectronic Millar catheter inserted below the dura, intracranialpressures were measured continuously in the spontaneously breathingpigs. Intrathoracic pressures (ITP) were recorded using a Millarcatheter placed in the trachea at the level of the carina. Afterstabilizing the pigs blood pressure, heart rate, and ventilation rate,intracranial pressures (ICP) and intrathoracic pressures were recorded,with 0 cmH2O inspiratory impedance and then with inspiratory impedancesof 5, 10, 15, and 20 cm H2O. Inspiratory impedance was achieved using animpedance threshold valve (ITV) as described in FIGS. 2-5.

At base, the intracranial pressure was approximately 8/4 mmHg. Withincreasing amounts of inspiratory impedance, the intracranial pressurewas lowered proportionally as shown in FIG. 7. The intracranial pressurewas 6/-2 mmHg when the pig breathed through an impedance of 20 cm H2O.These findings were observed in multiple pig studies and werereproducible. Next, the Millar catheter was inserted 3 cm into the pig'sbrain. The intracranial pressure increased secondary to the traumaassociated with the insertion of the probe. The intracranial pressureincreased to 25/22 mmHg at the new baseline. Next, the impedancethreshold valve was evaluated at different levels of resistance (FIG.8). Again, there was a decrease in intracranial pressure proportional tothe degree of inspiratory impedance.

Example 2

In this example, intracranial pressures were increased in the setting ofrecovery from cardiac arrest. The example used a pig model withventricular fibrillation for 6 minutes followed by cardiopulmonaryresuscitation for 6 minutes, followed by defibrillation. Spontaneousbreathing resulted in an up to 50% decrease in intracranial pressureswhen the animals breathed through an inspiratory impedance of 10 cm H2Ousing a valve system similar to Example 1.

In all examples above, the intrathoracic pressure decreased relative tothe rest of the body, creating a suction effect that reduced thepressure in the venous blood vessels draining the brain, therebyreducing intracranial pressures.

The invention further provides techniques and devices for reducingintracranial pressure (ICP) by facilitating movement of cerebral spinalfluid (CFS). There are a number of causes of increased ICP including:head injury, ischemia, osmolar imbalance, cerebral edema, tumors,complications of dialysis, infections, stroke, hypertensive crises. Eachcan result in a slow, and in some cases, an acute rise in the ICP. Thesolid matter of the brain contents makes up about 80-85% of the materialenclosed by the skull. Cerebral blood volume accounts for 3-6% and CSFfor 5-15%. See, Anesthesia, Third Edition Editor, Ron Miller. Chapterauthors: Shapiro and Drummond. Chapter 54 (1990), the completedisclosure of which is herein incorporated by reference. CSF moveswithin the brain from its site of production to its site of reabsorptionin the brain in an unimpeded manner under normal physiological states.Since the contents in the brain are practically incompressible, a changein volume of any one of the three major components (brain matter, bloodvolume, CSF volume) results in a reciprocal change in one or both of theother brain components. When the volume of the brain expands, secondaryto an increase in the non-CSF component(s), some of the CSF is forced toother locations, including through the foramen magnum (hole in skullconnecting skull to space where the spinal cord is located) and into theCSF fluid space surrounding the spinal cord. When the non-CSF componentsexpand in volume or size, the intracranial pressure rises. Normal ICPlevels are 10-15 mmHg when supine. At levels greater than 15-20 mmHg,damage to the brain can occur secondary to compression and resultanttissue ischemia (lack of adequate blood flow). A reduction in ICP levelscan be achieved by a number of clinical interventions including waterrestriction, diuretics, steroids, hyperventilation, a reduction ofcerebral venous pressure, hypothermia, CSF drainage, and surgicaldecompression.

Increased ICP results in reduced CSF fluid movement and translocation.CSF fluid production generally remains constant (about 150 ml/day)despite elevated ICP. CSF fluid reabsorption is can be slowed byelevated ICP. By using the valve systems described herein, centralvenous pressures may be reduced. In turn, this results in a decrease inICP and results in an increase in CSF fluid movement or translocationand reabsorption. This results in a further reduction in ICP.

The valve systems of the invention may be used in spontaneouslybreathing individuals, in patients ventilated with negative pressureventilation or in patients ventilated with a ventilator that causes adecrease in central venous pressures for at least a portion of therespiratory cycle. Each time the intrathoracic pressure is reduced withthe valve systems of the invention, there is a concomitant reduction inICP and an increase in the movement of CSF. In other words, there is anincrease in the difference between the peak and trough of the ICP waveform when using the valve systems. The sinusoidal movement occurs inspontaneously breathing people because of the change in pressure in thethorax that is transmitted to the brain via the venous blood vessels.The normally fluctuating CSF pressures (the pressure increases anddecreases with each inspiration) are altered by the valve systems. Morespecifically, the valve systems create a lower trough value therebycreating an overall created change in the ICP with each inspiration. Inthe non-breathing patient, a similar effect can be produced with thevalve systems when used with a variety of ventilator devices, includingan iron lung, a phrenic nerve stimulator (such as those described inU.S. Pat. Nos. 6,234,985; 6,224,562; and 6312399, incorporated herein byreference), a suction cup on the chest that is used to periodicallyexpand the chest and the like.

Increased CSF fluid movement results in an overall improved metabolicstate for the brain. This is shown schematically in FIGS. 9A and 9B. InFIG. 9A, the brain 400 is shown under normal conditions. The brain 400is surrounded by CSF 402 which is produced at a site 404. The CFS inturn is surrounded by the skull 406. Blood enters brain 400 through anartery 408 and exits through a vein 410. Vein 410 also includes a site412 of CFS drainage. Shown in FIG. 9A is an arrow showing the directionof CFS flow when draining. Extending from brain 400 is the spinal cord414 that is surrounded by the foramen magnum 416.

In FIG. 9B, the brain 400 is significantly swollen which reduces thespace 402 where the CFS is located. The swelling of the brain 400 cancause blockage of CSF to the spinal cord 414 as shown by arrow 418.Also, movement of CSF to site 412 is reduced to hinder movement of CSFout of the skull 406.

By treating the elevated ICP associated with all of the conditions notedabove using the valve systems described herein, brain swelling can bereduced. In so doing, CFS movement and fluid translocation is increasedunder those same conditions. This results in a further decrease inintracranial pressure as the CSF is able to relocate.

Referring now to FIG. 10, the effects of contracting the atria of theheart on ICP will be described. As shown, contraction of the atriaresults in a phasic movement in ICP. This can be most clearlydemonstrated during cardiac ventricular fibrillation. In that setting,the atria often beat spontaneously and the pressure of each contractionand relaxation waveform is transmitted immediately to the brain and isreflected in nearly identical fluctuations in ICP. The inventor hasdiscovered that the fluid systems (venous blood vessels and CSF) are soclosely linked, that subtle changes in the heart rhythm result inimmediate changes in CSF pressure. Thus, in some patients withsignificant heart rhythms, or significant heart failure, the rise inright heart pressures as a result of these conditions results in anincrease in ICP. Such rises in ICP can lead to a decrease in cerebralperfusion, since cerebral perfusion is determined by the pressure of theblood entering the brain (mean arterial pressure) minus the pressure ofthe blood leaving the brain (ICP and central venous pressure). Use ofthe valve and intrathoracic vacuum systems described herein will resultin a decrease in intrathoracic pressure. As shown in FIG. 10, thedownwardly pointing arrows represent the timing of each inhalationthrough the valve system. In the baseline state, before the onset ofatrial fibrillation, each inspiration (small arrows) results in areduction in ITP, a reduction of right atria pressure, a reduction incentral venous pressures, and then an immediate reduction in ICP. Withthe onset of atrial fibrillation, the intracranial pressure rises andthe sinusoidal pattern of ICP amplitude changes becomes dampened. Assoon as the animal begins to inspire through an inspiration impedance of−10 cm H2O there is an immediate decrease in intrathoracic pressure(ITP), an immediate decrease in right atrial (RA) pressures, and animmediate decrease in intracranial pressure (ICP) along with therestoration of a sinusoidal fluctuation in ICP with each inspiration.With elevated ICP, inspiration through the impeding means results in adecrease in ICP, increased cerebral spinal fluid flow, and a decrease incerebral ischemia secondary to increased cerebral perfusion. As such,the valve systems can used in patients with heart rhythms, such asatrial fibrillation, or patients with heart failure who have increasedICP in order to reduce their ICP, increase CSF fluid movement andtranslocation, and ultimately help them to improve their brain function.

Hence, the amount of inspiratory resistance, or the amount of negativeintrathoracic pressure generation (which may be generated using avariety of techniques) can be controlled or regulated by feedback frommeasurement of ICP, blood pressure, respiratory rate, or otherphysiological parameters. Such a system could include a closed loopfeedback system.

FIG. 11 is a flow chart illustrating another method for treating aperson suffering from head trauma associated with elevated intracranialpressures. In so doing, it will be appreciated that such techniques mayalso be used to treat those suffering from low blood pressure or thosein cardiac arrest, among others. The techniques are particularly usefulin cases where the person is not breathing, although in some cases theycould be used for breathing patients as well.

In a broad sense, when treating a person suffering from head trauma, aperson's intrathoracic pressure is lowered to decrease intracranialpressures. In turn, this assists in reducing secondary brain injury. Asshown in step 500, equipment may be coupled to the person to assist inlowering the person's intrathoracic pressure. A wide variety ofequipment and techniques may be used to decrease the intrathoracicpressure, including using a mechanical ventilator capable of extractingrespiratory gases, such as the one described in U.S. Pat. No. 6,584,973,a phrenic nerve or other muscle stimulator (with or without the use ofan impedance mechanism, such as those described in U.S. Pat. Nos.5,551,420; 5,692,498; 6,062,219; 5,730,122; 6,155,257; 6,234,916 and6,224,562) such as those described in U.S. Pat. Nos. 6,234,985;6,224,562; 6,312,399; and 6463327, an iron lung device, a thoracic vestcapable of pulling outward on the chest wall to create an intrathoracicvacuum similar to the effect of an iron lung, a ventilatory bag, such asthe one described in copending U.S. application Ser. No. 10/660,366,filed Sep. 11, 2003 (attorney docket no. 16354-005400), filed on thesame date as the present application, and the like. The completedisclosures of all these references are herein incorporated byreference. For breathing patients, a threshold valve as described aboveand that is set to open when about 5 cmH2O is generated during aninhalation may be used to enhance the person's negative intrathoracicpressure.

When the person is not breathing, a positive pressure breath isdelivered to the person as illustrated in step 502. This may be donewith a mechanical ventilator, a ventilatory bag, mouth to mouth, and thelike. This is followed by an immediate decrease in intrathoracicpressure. This may be done by extracting or expelling respiratory gasesfrom the patient's lungs as shown in step 504. Any of the techniquesdescribed above may be used to lower the intrathoracic pressure. Such areduction in intrathoracic pressure also lowers central venous pressureand intracranial pressure.

The vacuum effect during the expiratory phase may be constant, variedover time or pulsed. Examples of different ways to apply the vacuum aredescribed later with respect to FIGS. 12A-12C. The initial positivepressure breath may be supplied for a time of about 250 milliseconds toabout 2 seconds, and more preferably from about 0.75 seconds to about1.5 seconds. The respiratory gases may be extracted for a time that isabout 0.5 to about 0.1 to that of the positive pressure breath. Thepositive pressure breath may be delivered at a flow rate in the rangefrom about 0.1 liters per second to about 5 liters per second, and morepreferably from about 0.2 liters per second to about 2 liters persecond. The expiratory flow (such as when using a mechanical ventilator)may be in the range from about 0.1 liters per second to about 5 litersper second, and more preferably from about 0.2 liters per second toabout 2 liters per second. The vacuum may be maintained with a negativeflow or without any flow. The vacuum may be in the range from about 0mmHg to about −50 mmHg, and more preferably from about 0 mmHg to about−20 mmHg.

As shown in step 506, the process of delivering a positive pressurebreath and then immediately lowering intrathoracic pressures may berepeated as long as necessary to control intracranial pressures. Oncefinished, the process ends at step 508.

The manner in which positive pressure breaths and the vacuum are createdmay vary depending upon a particular application. These may be appliedin a variety of waveforms having different durations and slopes.Examples include using a square wave, biphasic (where a vacuum iscreated followed by positive pressure, decay (where a vacuum is createdand then permitted to decay), and the like. Three specific examples ofhow this may occur are illustrated in FIGS. 12A-12C, although others arepossible. For convenience of discussion, the time during which thepositive pressure breath occurs may be defined in terms of theinspiratory phase, and the time during which the intrathoracic pressureis lowered may be defined in terms of the expiratory phase. The positivepressure breaths may occur at about 10 to about 16 breaths per minute,with the inspiratory phase lasing about 1.0 to about 1.5 seconds, andthe expiration phase lasing about 3 to about 5 seconds. As shown in FIG.12A, respiratory gases are quickly supplied up to a pressure of about 22mmHg. This is immediately reversed to a negative pressure of about −10mmHg. This pressure is kept relatively constant until the end of theexpiratory phase where the cycle is repeated.

In FIG. 12B, the positive pressure is more slowly applied. When reachinga pressure of about 10 to about 15 mmHg, the pressure is rapidlyreversed to a negative pressure of about −20 mmHg. The negative pressuregradually declines to about 0 mmHg at the end of the expiratory phase.The cycle is then repeated. Hence, in the cycle of FIG. 12B, thepositive pressure is reduced compared to the cycle in FIG. 12A, and thenegative pressure is initially lower, but allowed to gradually increase.The technique is designed to help reduce a possible airway collapse.

In FIG. 12C, the positive pressure is brought up to about 20 mmHg andthen immediately brought down to about 0 mmHg. The negative pressure isthen gradually increased to about −20 mmHg toward the end of theexpiratory phase. This cycle is designed to help reduce a possibleairway collapse.

FIGS. 13A and 13B schematically illustrate one embodiment of a device500 that may be used to lower intrathoracic pressures in a non-breathingpatient. Device 500 comprises a housing 502 having an interface opening504 that may be directly or indirectly coupled to the patient's airwayusing any type of patient interface. Housing 502 also includes a vacuumsource interface 506 that may be in fluid communication with any type ofdevice or system capable of producing a vacuum. Also coupled to housing502 is a means to regulate the vacuum, such as a pressure responsivevalve system 508. Device 500 further includes a ventilation interface510 that may be used to provide a breath to the patient, if needed, whenthe vacuum is not applied.

In this embodiment, the vacuum may be provided by essentially any typeof a vacuum source, and the regulator may comprise an impedance valve,such as those described in U.S. Pat. Nos. 5,551,420; 5,692,498;6,062,219; 5,730,122; 6,155,257; 6,234,916; 6,224,562; 6,234,985;6,224,562; 6,312,399; and 6,463,327 as well as others described herein.To supply a breath, a variety of ventilation sources may be used, suchas, for example, a bag valve resuscitator, that is coupled to interface510. Device 500 may further include a mechanism 512 to inhibit thevacuum when delivering a breath to the patient from the bag valveresuscitator. Once the breath is delivered, mechanism 512 operates topermit the vacuum within the thorax to be reapplied. The mechanism 512used to turn off and on the vacuum source can include a slider switchthat moves to close off the branch in housing 500 having the vacuumsource as illustrated in FIG. 13B. However, other types of switches ormechanisms may be used. In some cases, the vacuum source may have acontroller that is configured to shut off the vacuum when the breath isadministered so that mechanism 512 is not needed. Also, a controller andappropriate sensors could be used to sense when the breath is deliveredand stopped so that mechanism 512 may be appropriately operated by thecontroller. After the breath is delivered, mechanism 512 moves back tothe position illustrated in FIG. 13A so that the vacuum may be suppliedto the patient. When the vacuum reaches a threshold amount, regulator508 operates to maintain the level of vacuum at about the thresholdamount.

FIGS. 14A and 14B illustrate another embodiment of a device 530 that maybe used to treat a patient. Device 530 operates using similar principlesas device 500 illustrated in FIGS. 13A and 13B. Device 530 comprises ahousing 532 having a patient interface 534 that may be coupled to thepatient's airway and a vacuum interface 536 that may be coupled to avacuum source. Housing 532 also includes a ventilation interface 538through which a positive pressure breath may be supplied. Also coupledto housing 532 is a vacuum regulator 540 that regulates the amount ofvacuum supplied to the patient. One example of a flow regulator that maybe used is described below with references to FIGS. 15A and 15B.However, it will be appreciated that any of the flow regulatorsdescribed herein may be used. Disposed within housing 532 is a flowcontrol device 542 that is used orchestrate gas flows through housing532. Flow control device 542 comprises a cylindrical member 544 that mayslide within housing 532 and includes a flow path 546 that permits gasflow between interfaces 534 and 536 when flow control device 542 is inthe position illustrated in FIG. 14A. Conveniently, a spring 548 orother biasing mechanism is used to hold flow control device 542 in thehome position illustrated in FIG. 14A. Flow control device 542 alsoincludes a flow path 550 illustrated by the arrow in FIG. 14A to permitgas flows between regulator 540 and interface 536. Hence, when in thehome position, a vacuum may be supplied through interface 536 whichlowers the person's intrathoracic pressure. If the vacuum becomes togreat, gas flows are permitted through regulator 540 to lower the amountof vacuum.

As illustrated in FIG. 14B, flow control device 542 also includes a flowpath 552 that passes from interface 538 to interface 534. This permits apositive pressure breath to be supplied to the patient through interface538. More specifically, as gasses are injected through interface 538,they flow into flow control device 542 causing it to move within housing532 and compress spring 548. In so doing, flow path 546 closes as itbecomes blocked by housing 532. Flow path 550 also closes, leaving onlyflow path 552 opened to permit the respiratory gases to flow to thepatient. When the positive pressure breath stops, spring 548 forces flowcontrol device back to the home position where the vacuum is once againsupplied to the patient.

Hence, when a vacuum is applied from interface 536, air is pulled out ofthe patient through interface 534 until the cracking pressure of theimpedance valve 540 is reached. At that point air passes throughimpedance valve 540 from the ventilation source at interface 538,thereby setting the limit of the vacuum achieved in the patient. Whenpositive pressure ventilation is delivered from the ventilation sourceat interface 538, the internal slider switch cylinder 542 moves downwardto close off the vacuum source, allowing for delivery of a positivepressure volume to provide a breath to the patient. Flow control device542 may include a cup-shaped opening 556 which helps to move the device542 along with minimal force applied. Once the breath has beendelivered, and there is no positive force delivered from the ventilationsource to the device 542, spring 548 pushes upwards, re-exposing thepatient to the vacuum source.

Device 530 may also include an optional pressure pop-off regulator 560.In the event that the vacuum source is too great, the pop-off regulator560 opens allowing for pressure relief above the desired vacuumpressure. The pop-off regulator 560 may be configured to open forpressures greater than about 20 to about 100 mmHg.

Although the devices illustrated in FIGS. 13 and 14 are shown withmechanical switching mechanisms (to turn the vacuum off and on), othersmay also be used, such as magnetic, electronic, or electrical. Otherkinds of possible switches include a ball valve, flapper valve, fishmouth valve, or other mechanical means as well as electric or electronicvalving systems, including a solenoid, to allow for temporary inhibitionof the vacuum once the positive pressure breath is delivered from theventilation source. Additional regulators can also be used on the vacuumsource to limit the flow or force of the vacuum. For example, the vacuumsource could be configured to provide a constant vacuum once a thresholdlevel has been achieved. In addition, the vacuum regulator and impedancevalves 508 and 530 may be variable or set at a fixed level of impedance.The vacuum source may also be a suction line or come from a venturedevice attached to an oxygen tank that could both provide oxygen to thepatient and a vacuum source. Further, the invention is not limited tousing an impedance valve, as shown, to regulate the vacuum. Multipleswitching and regulating means may be used instead. The ventilationsource is similarly not limiting and may include sources such asmouth-to-mouth, a bag-valve resuscitator, an automatic ventilator, andthe like.

FIGS. 15A and 15B illustrate flow regulator 540 in greater detail.Regulator 540 comprises a housing 570 having a patient port 572 and aventilation port 574. Optionally, a supplemental oxygen port 576 mayalso be provided. Gas may flow through housing 570 (between ports 572and 574) through one of two flow paths. The first flow path is blockedby a one way check valve 578 that comprises a check valve gasket 580 anda spring 582. The second flow path is blocked by a diaphragm 584.

In operation, a vacuum is experienced at patient port 572 as the vacuumsource draws a vacuum at port 536 (See FIG. 14A). When the vacuumreaches a threshold level, spring 582 compresses to move gasket 580downward, thereby creating a flow path as illustrated in FIG. 15B. Asthe vacuum is pulled, diaphragm 584 closes to prevent air from flowingthrough the other flow path. Gasket 580 remains spaced apart from theopening as long as the vacuum is at the threshold level. In this way,regulator 540 is able to maintain the vacuum at a constant level.

When ready to ventilate the patient, the vacuum is stopped andrespiratory gases are injected into port 574 and/or port 576. Thesegasses lift diaphragm 584 to permit the gases to flow to the patient.

Example 3

Example 3 is another non-limiting example illustrating how intracranialpressures and intrathoracic pressures may be lowered and systolicarterial pressure may be increased according to one aspect of theinvention. In this example, 30 kg pigs were anesthetized with propofol.Using a micromanometer-tipped electronic Millar catheter inserted 2 cmbelow the dura, intracranial pressures were measured in non-breathingpigs. Intrathoracic pressures (ITP) were recorded using a Millarcatheter placed in the trachea at the level of the carina. Systolicaortic blood pressures (SBP) were measured in the aorta with a Millarcatheter. To regulate intrathoracic pressures, a system similar to thatillustrated in FIGS. 14A, 14B, 15A and 15B was used, with inspiratoryimpedance (−8 cm H2O with a flow rate of 30 L/min). Positive pressureventilation was provided at a rate of 10 breaths/min with a tidal volumeof approximately 400 ml delivered over 1.0 seconds with an automatictransport ventilator. The objectives, methods, results, and conclusionsdescribing these novel cardiopulmonary-cranial interactions aresummarized below.

An objective of this example was to evaluate the acute use of a novelinspiratory impedance threshold device (ITD) attached to a controlledbut continuous vacuum (CV) source to decrease intrathoracic pressure(ITP) and intracranial pressure (ICP) but simultaneously increase meanarterial pressure (MAP), coronary perfusion pressure (CPP) and cerebralperfusion pressure (CerPP) in an apneic pig model of sequential insultsof cardiac arrest and fixed-bleed hemorrhage hypotensive shock. Thisanimal model is associated with both elevated ICP after cardiac arrestand significant hypotension after hemorrhage.

This example used 6 female farm pigs (28-32 kg) that were anesthetizedwith propofol, intubated and ventilated to maintain normocarbia and O2saturation >90%. Ventricular fibrillation was induced and followed by 6min of no treatment, 6 min of standard CPR, and then defibrillation.After return of spontaneous circulation and while ventilatedmechanically at 10 breaths/min, 35% of blood volume was removed with arate of 60 cc/min. Five min later ITD-CV was applied for 5 min alongwith positive pressure ventilation with 100% oxygen at a rate of 10 bpm.The ITD-CV was then removed and positive pressure ventilation at a rateof 10 breaths/min was reapplied. Hemodynamic parameters and arterialblood gases were assessed before, during, and after ITD-CV application.Statistical analysis was performed with a paired t-test and ANOVA tocompare +/−ITD-CV use.

The results are summarized in the Table below. As shown, by regulatingthoracic pressures, use of the ITD-CV causes an instantaneous decreasein ITP and ICP as well as a rapid rise in MAP and a marked increase inCerPP. Hence, the ITD-CV may be used to treat hypotension, shock, andcerebral hypertension.

TABLE Before ITD-CV During ITD-CV After ITD-CV p value ITP  0.5 ± 0.1−12.0 ± 1.1   0.1 ± 0.2 0.001 MAP 46.7 ± 5.2 54.7 ± 7.7 38.3 ± 4.1 0.03ICP 14.1 ± 3.9  6.1 ± 4.5 15.4 ± 3.9 0.001 CerPP 32.7 ± 4.2 48.6 ± 5.923.0 ± 4.5 0.01 CPP 40.1 ± 4.5 58.4 ± 7.7 31.1 ± 3.4 0.008

In one particular embodiment, a person may have his or her intrathoracicpressure manipulated using multiple techniques, alone or in combination.For example, some type of external thoracic positive pressure source maybe used to increase and then decrease the person's intrathoracicpressure to move blood out of and then into the heart and lungs in arepetitive fashion. Examples of such an external thoracic positivepressure source include a mechanical extrathoracic vest, a body cuirass,a compression piston, a compression cup, or the like. Such devices mayfunction as non-invasive hemodynamic support devices for maintenance ofincrease blood pressure and circulation in hypotensive patients.

While the person's intrathoracic pressures are being externallymanipulated (e.g., being increased and decreased), the person may alsohave his or her intrathoracic pressures manipulated by applying positivepressure breaths and a vacuum using any of the techniques describedherein. Further, any of the valve systems described herein may be usedin combination as well. Hence, while the person's chest is beingcompressed and relaxed, positive pressure breaths followed by a vacuummay be applied at the same time. In this way, non-invasive techniquesare provided for improving blood flow to the vital organs for anindefinite period of time, and may be used in cases where the patient isin shock, has very low blood pressure, those in cardiac arrest, and thelike. Also, such techniques may be used to circulate a preservativesolution, equivalent to cardioplegic agents, until more definitive careis available.

The timing of each of these steps may be controlled to correlate in anymanner, such as, for example, applying the vacuum while the force on thepatient's chest is relaxed. Also, the timing of chest compressions couldbe tied to other variables, such as timing the compressions and/ordecompressions with intrinsic cardiac rhythm (i.e., ECG activity).Further, the positive pressure breaths may be performed only as neededand not in association with every chest compression. Further, the chestmay be decompressed only after a certain number of chest compressions.

As with other embodiments, the patient may also be supplied withperiodic positive pressure ventilation or an extracorporeal oxygenatorto provide adequate respiration. Negative pressure ventilation may alsobe used to provide proper ventilation. For example, the chest may bedecompressed with an unimpeded airway to provide the negative pressureventilation. Also, the techniques just described could also be usedalone or in combination with invasive ways to also maintain bloodpressure. For instance, a greater effect on intracranial pressure may beproduced if some of the patient's blood is removed from the body.

One particular arrangement of a system that may be used with suchtechniques is set forth in FIG. 6 (previously described) where element370 (an iron lung cuirass device) may also schematically represent anyof the external thoracic positive pressure sources described herein.Further, controller 310 may also include some type of energy source foroperating the positive pressure source, such as pneumatic, electronic,combustion or the like. In this way, a variety of energy sources may beused to compress the chest and then release the compression in analternating manner. Ventilator 360 may be used to apply the positivepressure breath followed by a vacuum using any of the techniquesdescribed herein, as well as to provide proper ventilation. Further,although shown with valve system 200, it will be appreciated that any ofthe other valve systems described herein may be used as well. Also, itwill be appreciated that temperature sensor 350 may be substituted withother types of sensors and/or monitors, such as an ECG monitor, so thatchest compressions and/or decompressions may be timed with ECG activity.

The invention has now been described in detail for purposes of clarityand understanding. However, it will be appreciated that certain changesand modifications may be practiced within the scope of the appendedclaims.

1-40. (canceled)
 41. A medical method for treating a person, the methodcomprising: interfacing a threshold valve with the person's airway,wherein the threshold valve is configured to open when the person'snegative intrathoracic pressure reaches about −3 cm H2O to about −20 cmH2O to permit respiratory gases to flow into the person's airway;repetitively compressing the person's chest to provide a compressionphase where the chest is compressed and a decompression phase where thechest is actively lifted using an active chest compression/decompressiondevice; while repeatedly compressing and lifting the person's chest,extracting respiratory gases from the person's airway using a vacuumgenerated when actively lifting the chest with the active chestcompression/decompression device while the threshold valve is interfacedwith the person's airway to create an intrathoracic vacuum to lowerpressures in the thorax; wherein the level of the negative intrathoracicpressure is repetitively lowered over at least two successive chestdecompressions, and wherein use of the active chestcompression/decompression device and the threshold valve generates anintrathoracic pressure that rapidly decreases as the person's chest isactively lifted.
 42. A method as in claim 41, wherein the pressures arelowered in the thorax in order to lower intracranial pressures.
 43. Amethod as in claim 41, wherein the pressures are lowered in the thoraxin order to enhance cerebral perfusion pressures.
 44. A method as inclaim 41, further comprising at least periodically delivering a positivepressure breath to the person to provide ventilation.
 45. A method as inclaim 41, wherein the person is suffering from ailments selected from agroup consisting of elevated intracranial pressures, shock, low bloodpressure, low blood circulation, low blood volume, cardiac arrest andheart failure.
 46. A medical method for treating a person, the methodcomprising: interfacing a threshold valve with the person's airway,wherein the threshold valve is configured to open when the person'snegative intrathoracic pressure reaches about −3 cm H2O to about −20 cmH2O to permit respiratory gases to flow into the person's airway;repetitively compressing the person's chest to provide a compressionphase where the chest is compressed and a decompression phase where thechest is actively lifted using an active chest compression/decompressiondevice; while repeatedly compressing and lifting the person's chest,extracting respiratory gases from the person's airway using a vacuumgenerated when actively lifting the chest with the active chestcompression/decompression device while the threshold valve is interfacedwith the person's airway to create an intrathoracic vacuum to lowerpressures in the thorax; wherein the level of the negative intrathoracicpressure is repetitively lowered over at least two successive chestdecompressions.
 47. A method as in claim 46, wherein the pressures arelowered in the thorax in order to lower intracranial pressures.
 48. Amethod as in claim 46, wherein the pressures are lowered in the thoraxin order to enhance cerebral perfusion pressures.
 49. A method as inclaim 46, further comprising at least periodically delivering a positivepressure breath to the person to provide ventilation.
 50. A method as inclaim 46, wherein the person is suffering from ailments selected from agroup consisting of elevated intracranial pressures, shock, low bloodpressure, low blood circulation, low blood volume, cardiac arrest andheart failure.
 51. A medical method for treating a person, the methodcomprising: interfacing a threshold valve with the person's airway,wherein the threshold valve is configured to open when the person'snegative intrathoracic pressure reaches about −3 cm H2O to about −20 cmH2O to permit respiratory gases to flow into the person's airway;repetitively compressing the person's chest to provide a compressionphase where the chest is compressed and a decompression phase where thechest is actively lifted using an active chest compression/decompressiondevice; while repeatedly compressing and lifting the person's chest,extracting respiratory gases from the person's airway using a vacuumgenerated when actively lifting the chest with the active chestcompression/decompression device while the threshold valve is interfacedwith the person's airway to create an intrathoracic vacuum to lowerpressures in the thorax; wherein use of the active chestcompression/decompression device and the threshold valve generates anintrathoracic pressure that rapidly decreases as the person's chest isactively lifted.
 52. A method as in claim 51, wherein the pressures arelowered in the thorax in order to lower intracranial pressures.
 53. Amethod as in claim 51, wherein the pressures are lowered in the thoraxin order to enhance cerebral perfusion pressures.
 54. A method as inclaim 51, further comprising at least periodically delivering a positivepressure breath to the person to provide ventilation.
 55. A method as inclaim 51, wherein the person is suffering from ailments selected from agroup consisting of elevated intracranial pressures, shock, low bloodpressure, low blood circulation, low blood volume, cardiac arrest andheart failure.